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Cell Rep. 2016 Jun 28;16(1):186-200. doi: 10.1016/j.celrep.2016.05.070. Epub 2016 Jun 16.

Cytomegalovirus Restructures Lipid Rafts via a US28/CDC42-Mediated Pathway, Enhancing Cholesterol Efflux from Host Cells.

Author information

1
Baker IDI Heart and Diabetes Institute, Melbourne, VIC 3004, Australia.
2
Baker IDI Heart and Diabetes Institute, Melbourne, VIC 3004, Australia; Department of Medicine, Karolinska Institute, Stockholm 171 76, Sweden.
3
Discipline of Infectious Diseases and Immunology, University of Sydney, NSW 2006, Australia.
4
Department of Medicine, Karolinska Institute, Stockholm 171 76, Sweden.
5
Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA.
6
GW School of Medicine and Health Sciences, George Washington University, Washington, DC 20037, USA.
7
Baker IDI Heart and Diabetes Institute, Melbourne, VIC 3004, Australia. Electronic address: dmitri.sviridov@bakeridi.edu.au.

Abstract

Cytomegalovirus (HCMV) contains cholesterol, but how HCMV interacts with host cholesterol metabolism is unknown. We found that, in human fibroblasts, HCMV infection increased the efflux of cellular cholesterol, despite reducing the abundance of ABCA1. Mechanistically, viral protein US28 was acting through CDC42, rearranging actin microfilaments, causing association of actin with lipid rafts, and leading to a dramatic change in the abundance and/or structure of lipid rafts. These changes displaced ABCA1 from the cell surface but created new binding sites for apolipoprotein A-I, resulting in enhanced cholesterol efflux. The changes also reduced the inflammatory response in macrophages. HCMV infection modified the host lipidome profile and expression of several genes and microRNAs involved in cholesterol metabolism. In mice, murine CMV infection elevated plasma triglycerides but did not affect the level and functionality of high-density lipoprotein. Thus, HCMV, through its protein US28, reorganizes lipid rafts and disturbs cell cholesterol metabolism.

PMID:
27320924
PMCID:
PMC5389417
DOI:
10.1016/j.celrep.2016.05.070
[Indexed for MEDLINE]
Free PMC Article

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